The goal of the CBI Training Program is to provide students with the intellectual and technical skills that are necessary to solve important and complex biological problems that can be most effectively addressed by studies at the chemistry-biology interface. We have chosen to focus on the mechanistic chemistry of biomolecules since it is a theme that is of interest to a significant population of faculty and students on campus and provides an excellent model system for the application of tools at the chemistry-biology interface to solve important biological problems. The program will create a group of chemists and biologists who can speak the same language and thereby function effectively in multidisciplinary teams. The Program involves 34 participating faculty from The Wistar Institute and two separate Schools within the University of Pennsylvania, The Perelman School of Medicine and The School of Arts and Sciences. Participating students come primarily from two graduate groups that span institution and school boundaries, the Graduate Group in Chemistry and the Graduate Group in Biochemistry and Biophysics. To insure that students carry out research within the scope of the training program, students are selected for the program after they have chosen a thesis laboratory and project and generally at the start of their second year. To insure cross-fertilization between the chemistry and biology students, those selected for support by the training grant also participate in the following activities: (1) collaborative research at the chemistry-biology interface, (2) didactic course-work dealing with the chemistry and biology of proteins nucleic acids and small biomolecules, including a literature-based component, (3) a student-run trice-annual Chemical Biophysics mini-symposia series, (4) monthly student luncheons, (5) an annual Chemistry-Biology Interface retreat, (6) an annual mid-Atlantic Frontiers at the Chemistry-Biology Interface Symposium, and (7) a structured career development plan. The program also has effective mechanisms in place for the recruitment of underrepresented minorities as well as the disadvantaged and disabled, and for student instruction in the responsible conduct of research. We request funds for a steady state predoctoral training group of 9 students. A training committee is comprised of roughly equal faculty representation from the three participating programs and trainee representatives and meet every 6 months. The training committee is responsible for selecting students for training slot positions, insure equitable distribution of students, encourage application from underrepresented minorities, the disadvantaged and disabled and administer other functions of the grant.